Recent studies indicate the critical role of tumor associated macrophages (TAMs), tumor associated dendritic cells (TADCs), cytotoxic T lymphocytes (CTL), and other immunocytes in tumorigenesis and tumor progression. These cells can have a significant impact on the tumor microenvironment (TME) via their cell-to-cell direct effects, or indirect effects by production of cytokines and chemokines. Additionally, products secreted from all these cells have defined specific roles in regulating tumor cell proliferation, angiogenesis, and metastasis. They act in a protumorous capacity in vivo as evidenced by the recent studies indicating that dendritic cells, macrophages, T cells, and neutrophils may be manipulated to exhibit cytotoxic activity against tumors. Therefore, therapy targeting these cells may be promising, or they may constitute drug or anticancer particles delivery systems to the tumors (Cancer immunotherapy: Multi-pronged tumour attack. Nature 28 Vol. 538, 431, 2016).
As a nature's adjuvant and professional antigen-presenting cells (APCs), dendritic cells (DCs) play a central role of immune system ability to react against cancer cells. The principle of DC therapy is to exploit basic ability of DCs to stimulate T cell-based anticancer response. The most important process is the ability of DCs to cross-present antigens with immunostimulatory potential, which relies on presentation of exogenous antigens (normally presented on MHC class II) via MHC class I, enabling direct CD8+ T cell stimulation for anti-tumor immune responses (Cancer immunotherapy via dendritic cells, Nature Reviews Cancer Vol. 12, 265-277, 2012). Most of the therapeutic protocols use monocyte-derived DCs (moDCs), which require their differentiation into immature DCs and subsequent maturation to DCs with anti-tumor function. It should be mentioned that not all mature (or activated) DCs are equivalently immunogenic with anti-tumor function. The biomarkers of functional maturation of DCs with anti-tumor immune response are CD80, CD83, CD86, CD103. The choice of differentiation protocols is absolutely crucial for maximizing immunostimulatory potential of monocyte-derived DCs (moDCs). Most of the protocols use IL-4 and GM-CSF. However, this classical method can be improved as shown by replacement of IL-4 with IL-15 or IFNα.
Tumor associated macrophages (TAMs) are the major players in the tumor microenvironment, and high TAM presented in tumors is associated with a poor prognosis for cancer patients. Based on biological functions, macrophages are divided broadly into two phenotypes: classical M1 and alternative M2 macrophages. The M1 macrophages are driven by the Th1 cytokine interferon-γ, bacterial moieties, and Toll-like receptor (TLR) agonists, and characterized by the production of pro-inflammatory factors such as IL-6, IL-12, IL-23, and tumor necrosis factor-α (TNF-α). Thus, M1 macrophages are involved in the inflammatory response and antitumor immunity. Conversely, the M2 macrophages are associated with Th2 cytokines (IL-4, IL-10, IL-13), and related to an anti-inflammatory response, wound healing, and pro-tumorigenic properties. In general, TAMs resemble the M2 macrophages and M2-like TAMs are critical modulators of the tumor microenvironment for tumor progression (including tumor proliferation, angiogenesis/vasculogenesis, metastasis, and evasion and subversion of host immunosurveillance) and therapeutic resistance (Diverse macrophages polarization in tumor microenvironment. Archives of Pharmacal Research, pp 1-9, 2016). Thus, in addition to be a potentially useful prognostic marker of clinical outcomes, reprogramming of the TAMs from M2 phenotype to M1 phenotype is an important issue in anti-tumor immunotherapy and inhibition of tumor progression.
U.S. Pat. No. 8,728,543 discloses a method of treating idiopathic thrombocytopenic purpura in a human in need thereof, comprising administering a therapeutically effective amount of an extract of Astragalus membranaceus to said human.
U.S. Pat. No. 9,139,652 teaches a method for increasing a patient's pool of M1 macrophages, wherein said method comprises administering to the patient a monoclonal antibody, capable of binding to colony-stimulating factor-1 receptor, in an amount effective to increase the patient's pool of M1 macrophages.